Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins


Kim, M., Carman, C.V. & Springer, T.A. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 301, 5640, 1720-1725 (2003).
Kim_2003Suppl_15919.pdf662 KB

Date Published:

Sep 19


Although critical for development, immunity, wound healing, and metastasis, integrins represent one of the few classes of plasma membrane receptors for which the basic signaling mechanism remains a mystery. We investigated cytoplasmic conformational changes in the integrin LFA-1 (alphaLbeta2) in living cells by measuring fluorescence resonance energy transfer between cyan fluorescent protein-fused and yellow fluorescent protein-fused alphaL and beta2 cytoplasmic domains. In the resting state these domains were close to each other, but underwent significant spatial separation upon either intracellular activation of integrin adhesiveness (inside-out signaling) or ligand binding (outside-in signaling). Thus, bidirectional integrin signaling is accomplished by coupling extracellular conformational changes to an unclasping and separation of the alpha and beta cytoplasmic domains, a distinctive mechanism for transmitting information across the plasma membrane.

Last updated on 09/30/2015